The present invention relates to methods of treatment and instruments for the control of halitosis-generating and other microorganisms in the non-dental upper respiratory tract. More particularly the methods and instruments of the invention are useful for the control of chronic or low-level infections of bacteria or other microorganisms causing halitosis, sinusitis and other chronic conditions. Many people suffer persistent chronic halitosis, being bad or malodorous breath, which can often be diagnosed as being attributable to resilient colonies of bacteria that have become established in posterior oral locations such as the back of the tongue and the tonsils. As is well known, the affliction of halitosis (bad breath) may constitute a serious problem, particularly in social situations. Halitosis can be quite severe and it may occur occasionally or chronically or regularly, for example at specific times of the day or month.
Studies on the etiologies of breath malodor indicate that volatile sulfur compounds (“VSCs”) which have unpleasant odors, even in extremely low concentrations, are the principal odorants in bad breath. Some examples of such VSCs are hydrogen sulfide, mercaptans, methyl mercaptan, dimethyl sulfides, skatole, cadaverine, putrescine and isovaleric acid. Such volatile sulfur compounds may originate from the anaerobic bacterial degradation, notably by anaerobic Gram-negative bacteria, of sulfur-containing amino acids within the oral cavity. However, the bacteria responsible for halitosis have not as yet been fully elucidated.
As described by C. E. Kazor et al. in “Diversity of Bacterial Populations on the Tongue Dorsa of Patients with Halitosis and Healthy Patients” Journal of Clinical Microbiology, February 2003, p. 588-563, the oral cavity of normal, healthy humans i bacterial species. These bacteria form a unique ecosystem with complex interactions and interdependencies between species with some bacteria producing substrates consumed by other bacteria. Environmental factors, such as diet or decrease of host immune resistance may lead to the overgrowth of unfavorable species for example Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Treponema denticola, Actinobacillus actinomycetemcomitans and Bacteroides spp whose presence as significant populations may be associated with health disorders or disease conditions.
Some such conditions include chronic periodontitis, that is a major cause of tooth loss in adults when unfavorable species inhabit the periodontal pockets and halitosis (or bad breath) associated with the presence of unfavorable species on the back and base of the tongue. Conventionally, antibiotics are used to treat offending bacteria associated with conditions sufficiently severe to be inflammatory. Nevertheless, in chronic bacterially induced conditions there may be severe disadvantages to the long-term use of pharmacological antimicrobial agents, either systemically or topically. Possible drawbacks include the development of resistance rendering the agents clinically ineffective and disruption of the normal oral microflora present in healthy individuals. Gastrointestinal disturbances may also be associated with use of antibiotics.
As described by Wilson et al. in Int. Dent. J. 44:181-189, many therapeutic regimens used for oral infections eliminate both pathogenic and commensal organisms indiscriminately, thereby disrupting the natural ecosystem of the oral cavity. According to Kazor et al., certain bacterial species are significantly associated with halitosis for example Atopobium parvulum, Eubacterium sulci, Fusobacterium periodonticum, a phylotype (clone BS095) of Dialister, a phylotype (clone BW009) of Streptococcus, a phylotype (clone DR034) of the uncultivated phylum TM7 (8), and Solobacterium moorei. (See FIG. 1 and Table 2.) Some other species that have been associated with halitosis include Porphyromonas gingivalis, Fusobacterium nucleatum, Bacteroidesforsythus, Treponema denticola, Actinobacillus actinomycetemcomitan and Prevotella intermedia. 
Some species are also described as being associated with good health for example Streptococcus salivarius, Rothia mucilaginosa (Stomatocossus mucilaginosus), and an uncharacterized, cultivable species of Eubecterium (strain FTB41) (See FIG. 1 and Table 2). In contrast, S. salivarius was reportedly detected in only one of the subjects with halitosis and was detected at very low levels.
There exists a large market for mouthwashes, mouth rinses, dentifrices, chewable, gums and the like and other dental application products for oral hygiene use many or most of which are intended to control halitosis and which have varying degrees of effectiveness.
Antiseptic materials such as chlorhexidine, cetylpyridinium chloride, benzalkonium chloride, thymol eucalyptol, methyl salicylate, benzoic acid, boric acid, menthol, sanguinarine chloride and others are intended to control the formation of bacterial plaque. Antibiotics, such for example as metronidazole may also be employed. Herbal treatments for halitosis, including parsley, mint or olive oils or the like, have also been proposed. See for example Alvarez Hernandez U.S. Pat. Nos. 6,555,093 and 6,350,435.
For example, Ratcliff U.S. Pat. No. 4,689,215 discloses a treatment for halitosis wherein the oral cavity is rinsed with an aqueous solution of what is known as “stabilized chlorine dioxide”, a substance which provides a source of sodium chlorite, a precursor to chlorine dioxide which may be active against causative bacteria.
More recently, Witt, et al. U.S. Pat. No. 6,264,924 disclose use of a chewing gum containing small amounts of chlorite ion for antimicrobial and tooth whitening effects.
Also, for example, as disclosed in Pedersen U.S. Pat. No. 6,607,711, it has been proposed to employ chelated zinc in oral hygiene compositions intended to control halitosis.
Notwithstanding a wide range of available remedies such as the foregoing, it has been estimated that as many as 20-90 million people in the United States continue to be afflicted with the embarrassment and distress of halitosis, possibly because of the failure of such remedies to be fully effective. Pursuant to the present invention, it can be understood that such ineffectiveness may be attributable to the transient presence of the remedies in the vicinity of the bacteria, to the failure of the topically applied treatments to penetrate tissue surfaces and to biochemical resistance to the applied treatments and to the need for continual repetition of the treatments.
Some proposals for halitosis treatment recognize and address bacterial infection of the tonsils as a causative agent. For example, Hall U.S. Pat. No. 6,475,172 discloses a tonsil cleansing tool for removing food debris from a tonsillar pit by applying pressure to a surface of the tonsil close to the debris.
As described by Hall, human tonsils comprise a number of small lymphoid tissue organs located in a ring around the pharynx where they protect the entrance to the throat, namely the two palatine tonsils on each side of the tongue, the lingual tonsil at the back of the tongue and the pharyngeal tonsils, or adenoids, at the back of the pharynx. The tonsils are generally almond shaped and spongy textured, having small pits or cavities at their surfaces which are intended to collect invading microorganisms but which may also collect and harbor small food particles and sinus drainage and other debris which materials provide a substrate for microbial colonization and proliferation. Anaerobic bacteria generating malodorous VSCs can readily become established in these favorable locations, providing persistent sources of bad breath that are difficult to control or eradicate.
The tonsils are accordingly of particular interest as treatment targets for the processes of the invention in cases of halitosis. The tonsils are locations that may harbor persistent colonies of anaerobic bacteria and other microorganisms. Prescription of systemic antibiotics may be deemed unwise for a condition not regarded as presenting substantive risk of developing more serious pathologies or, if acceptable, may provide only short term control, with the unpleasant symptoms again presenting themselves within a few weeks or months of the initial relief. Alternatively, the bacterial colonies may be, or become resistant and antibiotics may have little if any effect. Use of antibiotics may eliminate susceptible strains providing opportunities for resistant strains to proliferate.
Orally administered topical agents, mouthwashes and the like may bring too little active agent to the site of infection for too short a period to be wholly effective. Neither systemic nor topical antibiotics are likely to be effective against viral or fungal infections which may be present as predominant or component microorganisms in the infection. Comparable considerations may apply to other infections of the nondental upper respiratory tract, such as nasal and sinus mucous tissues or cavities, for which there are ongoing needs for more effective simple treatments.
Various methods are also known for the treatment of bodily infections on internal surfaces which employ radiant energy as an alternative to antibiotic or chemical agents.
For example, Ganz U.S. Pat. Nos. 6,491,618 and 6,464,625 disclose methods and apparatus employing ionizing radiation, for example, ultraviolet light or x-ray radiation for treating gastrointestinal ailments of a patient including gastritis, gastric ulcer, duodenal ulcer, gastric cancer, gastric lymphoma, ulcerative colitis, or Crohn's disease. Such treatments are usually quite drastic and may not be suitable for treatment of chronic oral conditions. Tissue damage and inflammation as well as destruction of desirable commensal microbiotic species, may be induced by long-term application of such treatments. Furthermore, employment of short wavelength radiation risks DNA damage and possible carcinogenicity.
Other radiative treatments that have been employed for treating human microbiotic infections include photodynamic therapy. Photodynamic therapy is a relatively recent treatment method whose primariy applications have employed laser light to destroy tumor cells. The laser energy is targeted to the pathologic cells by staining the cells with specific dyes that have energy absorption peaks overlapping the laser energy wavelength whereby tumor cells absorb more laser energy than normal cells.
For example, Biel U.S. Pat. No. 6,159,236 discloses a medical device including a tube and expandable member which emits light for photodynamic therapy to treat internal body surfaces such as the larynx or cheek in order to treat or detect pathologies such as cancer and microbiological pathogens. An integrated array of vertical cavity surface emitting lasers (VCSEL) can provide a light emitting source for photodynamic therapy (“PDT”) treatment. Light is transmitted through an expandable member or balloon, which is inflated by air or a fluid, possibly a proteinaceous light-diffusing gel. The expandable member conforms with the surface to be treated.
Azar et al. United States Patent Application 20010024777 discloses another radiative energy treatment employing a toothbrush-like apparatus for self use to effect photothermolysis of oral plaque bacteria sensitized by staining. The apparatus functions to direct light on to at least one tooth. In order to avoid coagulation of blood vessels, light wavelengths near oxyhemoglobin absorption peaks are avoided, e.g. by filtration of the applied energy. Other biomedical applications of photothermal energy include external topical application especially for depilation, hair removal, for example, as disclosed in Azar and Shalev U.S. Pat. No. 6,187,001 and Azar U.S. Pat. No. 6,214,034. Kreindel U.S. Pat. No. 6,702,808 discloses use of light in combination with RF energy for treating hair, vascular lesions and other complex targets on the skin.
It is also known that electromagnetic radiation can be employed to destroy different types of bacteria, for example, Phoenix et al. in “The Phototoxicity Of Phenothiazinium Derivatives Against Escherichia Coli And Staphylococcus Aureus” FEMS Immunol Med Microbiol. 2003 Oct. 24; 39(1): 17-22 teach that phenothiazinium derivatives like methylene blue and toluidine blue O can cause bacterial cell death in both gram negative (E. Coli) and gram positive (Staph aureus) bacteria by phototoxicity when employed at “micromolar concentrations, levels much lower than those used in the topical and intravenous administration of a number of phenothiazinium compounds”. Illumination is effected by placing microtiter plates in a light box. Phoenix et al. suggest the tested dyes could be “useful in the phototherapy of localised bacterial infections, burn injuries for example.”
Animal studies have also been used to suggest human treatments. Teichert et al., in “Treatment of oral candidiasis with methylene blue-mediated photodynamic therapy in an immunodeficient murine model.” Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002 February; 93(2): 155-60, described evaluating the efficacy in an immune-compromised murine model of using methylene blue-mediated photodynamic therapy. This is a narrow-focus treatment of a single target fungal organism, oral candidiasis, a pathogen commonly afflicting immune-compromised AIDS patients. The authors reported that methylene blue concentrations of 450 and 500 microgram/mL activated with diode laser light at 664 nm using a cylindrical diffuser at 275 J/cm fiber length at 400 mW for 687.5 seconds, were able to “totally eradicate” Candida albicans in an immunosuppressed murine model. Teichert et al. professed to be the first to use antimicrobial photodynamic therapy “PDT” in an animal model and to treat oral candiasis by using a methylene blue-mediated photodynamic therapy. Teichert et al. suggests methylene blue-mediated PDT of oral candidiasis as a potential treatment alternative to traditional antifungal drug therapy.
Teichert et al.'s teachings regarding the response of a single fungal species in abnormal, immune-compromised mice do not suggest a solution to the problem of providing a treatment that can be directed against a broad-spectrum of bacterial populations in diversified members of the human population most of whom may have normal immunity. Furthermore, Teichert et al.'s treatment is time-consuming having a duration of 687.5 seconds (page 156, right hand column), about 11.5 minutes, and is intended to be applied only to a specific acute care patient group, AIDS patients, rather than to segments of the population that may largely be in moderate to good health.
Wilson et al. U.S. Pat. No. 5,611,793 discloses use of laser light in combination with a photosensitizing agent to disinfect or sterilize oral cavity tissues, wounds or lesions. Wilson's disclosed uses are dental or dentally related and include disinfecting and sterilizing dental tissues, gingival tissues and drilled-out carious lesions prior to filling, destroying cariogenic microbes on a tooth surface, treatment or prevention of chronic periodontitis and inflammatory periodontal diseases; treating oral candidiasis in AIDS patients, immuno-compromised patients and patients with denture stomatitis. Nondental applications are not suggested.
None of the foregoing proposals describes a simple and safe, non-chemical, broad-spectrum treatment of upper respiratory tract infections, including halitosis, in diverse human populations largely comprising otherwise healthy individuals, and which is suitable for repeated application to treat chronic conditions. Furthermore, many, if not all, known treatments act largely superficially and may fail to reach organisms lodged more deeply beneath the epithelial surface.
Accordingly, there is a general need for simple, more effective treatments of infections of nondental upper respiratory mucous tissues and specific needs for improved treatments of halitosis, sinus and nasal infections, for treatments which will be effective against Gram-negative bacteria and for deep treatments that can penetrate to organisms harbored beneath exposed surfaces.
The foregoing description of background art may include insights, discoveries, understandings or disclosures, or associations together of disclosures, that were not known to the relevant art prior to the present invention but which were provided by the invention. Some such contributions of the invention may have been specifically pointed out herein, whereas other such contributions of the invention will be apparent from their context. Merely because a document may have been cited here, no admission is made that the field of the document, which may be quite different from that of the invention, is analogous to the field or fields of the present invention.